POS0424 THE ROLE OF IL-25 REGULATING IL-17 AND ROR-γt ON Th17 IN RHEUMATOID ARTHRITIS
Authors: D. Liu, Y. LV
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is a prevalent common autoimmune disease characterized by chronic inflammation of the joint and synovial hyperplasia and progressive destruction of articular cartilage and bone, which seriously influences a patient’s quality of life.Interleukin-25 belongs to the IL-17 cytokine family newly identified. IL-25 is widely produced between tissues, IL-25 is reported to play an anti-inflammatory role in autoimmune and inflammatory diseases through the downregulation of Th1 and Th17 cell responses[1]. However, the exact role of IL-25 in the pathogenesis of RA remains to be elucidated. Objectives Set up CIA model to evaluated IL-25 influence in RA disease. Discuss the molecular mechanism of IL-25 how to regulate IL-17A, ROR-γt and Th17. Methods ①male DBA/1 mice (n=12) were induced with immunized intradermally twice with type II chick collagen (2 mg/ml) emulsified in Complete Freund’s adjuvant or Incomplete Freund’s adjuvant containing by tail intravenous injection.CIA mouse model was constructed. CIA were then divided into two groups, for the use of PBS (n=6) and IL-25 (0.5μg, n=6) respectively, and follow-up daily. After 42 days, mice were sacrificed and collected articular tissues, proceed pathological staining and pathological score of arthritis. ②Male DBA/1 mice were immunized with CII to induce arthritis and consecutively received rmIL-25 (1 μg/mice) or PBS for 5 days beginning from day 1 after the second immunization with CII, and the incidence of arthritis was calculated. Spleen CD4 + T cells were isolated from CIA mice using Mouse CD4 + T Cell Isolation Kit. Cells were stimulated with plate-bound anti-CD3 (5 μg/ml) plus anti-CD28 (2 μg/ml) in the presence or absence of recombinant mouse (rm) IL-25 (100 ng/ml) for 24 h. In some cases, control IgG (10 μg/ml) were added to the cultures. The expression of IL-17A were examined using ELISA assay and ROR-γt mRNA in the cells were measured by real-time quantitative qPCR. Results In vivo studies indicated that, the RA incidence and symptoms of arthritis in IL-25-treated mice were significantly reduced compared with PBS controls. Histopathologic examination showed that the knee joints of IL-25-treated mice with CIA exhibited a significant reduction in synovial hyperplasia, cartilage damage and bone erosion compared with PBS controls. The serum levels of IL-17A in IL-25-treated mice were markedly reduced compared with those in WT mice. RT-qPCR also demonstrated that the transcription levels of IL-17A and ROR-γt were decreased in the Spleen of IL-25-treated mice. Conclusion Systemic injection of IL-25 can reduce the onset of arthritis and joint injury in CIA mice. IL-25 can inhibit Th17 cells of CIA mice, and its target is to regulate IL-17 cytokines and Expression of ROR-γt mRNA. CIA protection is mediated by the inhibition of Th17 by IL-25. References [1]Fabien L, Ndongo-Thiam Ndiby the inhibition of Th17 by IL-25.d joint injury in CIA micnti-inflammatory Effects by Acting As a Receptor Antagonist for Interleukin-17A Function[J]. Frontiers in Immunology, 2017, 8:647. Disclosure of Interests None declared.